The overall objective of this proposal is to elucidate the inflammatory role of immune complexes trapped in joint collagenous tissues of patients with chronic inflammatory arthritides. It is proposed to study the interactions between trapped immune complexes in cartilage explants in organ culture and the cells known to be present in the rheumatoid pannus (lymphocytes, monocyte/macrophages and fibroblasts). The role of these interactions in cartilage breakdown will be delineated using organ culture systems designed to study cartilage matrix proteoglycan and collagen degradation. The autoantibody specificity of immune complexes trapped in rheumatoid and osteoarthritis articular cartilage will be investigated. Cartilage extracts will be tested for the presence of rheumatoid factors and anti-collagen antibodies. The relative enrichment of these auto-antibodies with respect to serum and synovial fluids will be determined. Comparison of antibody avidities between cartilage extracts, sera and synovial fluids will be made. Based on our previous studies demonstrating the in vitro generation of IgG aggregates by myeloperoxidase, H2O2 and a hydrogen donor such as catechol, we propose to inquire if this biochemical reaction can be demonstrated with phagocytic cells in vitro. In addition, we will investigate their appearance in inflammatory processes by analyzing complexes obtained from human and animal sera and synovial fluids.